Objective: Few real-world studies have shown clear association between interleukin (IL)-17 inhibitors and inflammatory bowel disease (IBD) onset. This study investigated the reporting prevalence and evaluated the clinical features and management of IL-17 inhibitor-related IBD events.Methods: We used the US FDA Adverse Event Reporting System database and retrieved data, from 2015 to 2022, on IL-17 inhibitors to identify gastrointestinal inflammatory events and conduct disproportionality analyses by estimating the reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs). Furthermore, case reports and case series, from 2015 to 30 November 2022, on IBD induced by IL-17 inhibitors were collected for retrospective analysis.Results: A total of 388 cases of primary suspected IL-17 inhibitor-associated gastrointestinal events were reported (268 IBD and 120 colitis), including 348 cases involving secukinumab (SEC), 36 cases involving ixekizumab (IXE), and 4 cases involving brodalumab (BRO). Statistically significant reporting rates of total IBD events were observed for SEC and IXE (ROR = 2.13, 95% CI [1.96-2.30] and ROR = 2.79, 95% CI [2.39-3.27], respectively), whereas BRO did not trigger a safety signal. Twenty-nine studies, which included 34 cases, showed evidence of IBD, following SEC (79.4%) and IXE (20.6%) treatment. The median age was 42 years; typical initial symptoms included diarrhea (90.9%), abdominal pain (57.6%), bloody diarrhea (51.5%), and fever (36.4%). The median time to onset of IBD symptoms was 2.9 months. Some cases were accompanied by elevated white blood cell (WBC) count (87.5%), erythrocyte sedimentation rate (ESR; 85.7%), C-reactive protein (CRP; 100%), and fecal calprotectin (FC; 100%). Cessation of IL-17 inhibitors plus treatment with corticosteroids and TNF antagonists, as either monotherapy or in combination, could lead to complete clinical remission. The median time to remission after IL-17 inhibitor discontinuation was 4 weeks.Conclusion: IL-17 inhibitor treatment is associated with exacerbation and new onset of IBD and colitis. Obtaining a detailed patient history before initiation of treatment and monitoring gastrointestinal symptoms and intestinal inflammatory biomarkers during IL-17 inhibitor treatment is important for safe use of these drugs.
Objective To analyze and discuss the clinical characteristics of dipeptidyl peptidase-4 inhibitor (DPP4i)-induced bullous pemphigoid (BP). Data Sources We collected case reports of DPP4i-induced BP by searching databases from 2006 to mid-May 2021, as a retrospective analysis. Study Selection and Data Extraction Relevant case reports and case analyses of DPP4i-induced BP were included. Data Synthesis The median time of symptom onset was 9 months (range 0.5-59 months). BP most often occurred in patients receiving vildagliptin (52.63%) followed by linagliptin (27.19%) and sitagliptin (17.54%). Tense bullae and blisters (85.51%) and erythema (82.61%) on the extremities and trunk were the most common presenting symptoms. In total, 64.06% of BP patients were anti-BP180 autoantibody positive, 58.97% were BP180NC16a autoantibody positive, and 31.25% were anti-BP230 autoantibody positive. Skin biopsy revealed subepidermal bulla eosinophil infiltration in 93.85% of BP patients, lymphocyte infiltration in 56.93%, and neutrophil infiltration in 44.62%. Direct immunofluorescence was positive in 98.94% of BP patients with linear deposition of IgG (97.80%) and/or complement C3 (98.94%) along the basement membrane zone. Indirect immunofluorescence was positive in 87.88% of BP patients. Complete remission of BP was achieved in 83.64% of patients on DPP4i withdrawal and after 4 months (range 0.13-72 months) of follow-up. Relevance to Patient Care and Clinical Practice This review analyzes and discusses the clinical characteristics of DPP4i-induced BP and provides a reference for the safe and reasonable clinical application of DPP4i. Conclusions DPP4i drugs are related to the occurrence of BP in diabetic patients, especially elderly men taking vildagliptin.
Ferroptosis-related genes (FRGs) have been identified as potential targets involved in oncogenesis and cancer therapeutic response. Nevertheless, the specific roles and underlying mechanisms of FRGs in GBM and temozolomide (TMZ) resistance remain unclear. Through comprehensive bioinformatics, we found that ferroptosis-related Fanconi anemia complementation group D2 (FANCD2) was significantly up-regulated in GBM tissues, and the high expression level of FANCD2 was related to the poor prognosis in primary and recurrent GBM patients. Furthermore, FANCD2 could promote TMZ resistance by attenuating ferroptosis in GBM cells. Knockdown of FANCD2 could increase reactive oxygen species (ROS) levels and inhibit cell survival. The two characteristics were associated with ferroptosis in TMZ-resistant GBM cells T98G-R and U118-R. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that aberrantly expressed FANCD2 was potentially linked with several cancer-associated signaling pathways, including chromosome segregation, DNA replication, and cell cycle transition. In addition, we demonstrated that FANCD2 expression was positively correlated with several tumor-infiltrating lymphocytes (TILs) and multiple immune-associated signatures in GBM. Therefore, up-regulated FANCD2 could protect GBM cells from ferroptosis and promote TMZ resistance. FANCD2 may be a novel therapeutic target in GBM.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.